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J F Westphal

Publications and source records attributed to J F Westphal.

25 records · Page 2Linked to original sources
PubMed1991

Reappraisal of amoxycillin absorption kinetics.

Interest in the intestinal absorption mechanisms of drugs has increased because transepithelial passage across the gut does not necessarily follow a passive diffusion process. Amoxycillin, like other amino-beta-lactam antibiotics, has been demonstrated in vitro to use the dipeptide carrier-mediated system in rodent small intestine. In order to assess the in-vivo relevance of these data, we applied the Loo-Riegelman method for a reappraisal of amoxycillin absorption kinetics in healthy human volunteers. The results showed evidence of a saturable carrier-mediated uptake of this antibiotic. With respect to the in-vitro data previously published, the dipeptide carrier system would appear to be the most likely transport mechanism.

Administration, Oral↗
PubMed1991

[Experimental study on the hepatobiliary kinetics and excretion of temafloxacin. Evidence for production of active metabolites by the rabbit liver].

Temafloxacin is a new fluoroquinolone derivative currently under evaluation. Its hepatobiliary disposition remains undefined as yet. The present study represents an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for three hours with reconstituted and oxygenated blood in a closed circuit. A the onset of the procedures, temafloxacin 10 mg were added to the circulating blood. Both bile and blood were sampled throughout the perfusion time, and liver fragments were taken at the end of the experiments. Temafloxacin levels were measured by HPLC in serum and hepatic tissue, and by both HPLC and microbiological assay in bile. The percentage of drug undergoing hepatic biotransformation appeared to be high, i.e. 58.3%. This finding is substantiated by the comparison of temafloxacin levels in bile, as provided by HPLC and microbiological assay, the latter yielding concentrations twice as high (biliary peak: 33.5 +/- 2.8 micrograms/ml versus 19.3 +/- 3.1 micrograms/ml by HPLC assay) as those obtained by HPLC (p less than 0.05). Consistently, the average amount of temafloxacin excreted into the bile (0-3 h) was, respectively, 92 micrograms (0.9% of the dose) and 204 micrograms (2.0%) as determined by HPLC and microbiological methods (p less than 0.05); this statistically significant difference suggests the presence of active metabolites in bile. The presented results bring out evidence for substantial biotransformation of temafloxacin by Rabbit liver. Extrapolation to other species, however, would be hazardous; further pharmacokinetic studies are needed in order to assess the relevance of these findings in humans.

4-Quinolones↗
PubMed1990

[Cefuroxime axetil, a new oral cephalosporin for treating infections of the ORL field: clinical synthesis].

Cefuroxime axetil (C.A.E.) is a broad spectrum cephalosporin, suitable for oral route. Its antibacterial activity includes all the pathogens usually responsible for E.N.T. infection, with low M.I.C.'s: H. influenzae, S. pneumoniae, S. aureus, S. pyogene. The stability of the drug against betalactamases, especially those produced by H. influenzae, associated with good bio availability (50%) and tissue penetration (30%) account for the potent in vivo bactericidal activity and clinical efficacy of cefuroxime axetil. More than 1,000 patients had been enrolled in controlled clinical trials: the success rates yielded by C.A.E. were 98%, 96% and 91%, respectively for pharingitis/tonsilitis, otitis media and acute sinusitis. C.A.E. is at least as effective as amoxycillin/clavulanic acid and safety appears to be better.

Cefuroxime↗
PubMed1990

Biliary elimination and hepatic disposition of a new fluoroquinolone, temafloxacin: experimental evaluation.

Temafloxacin is a new quinolone derivative presently under evaluation. Its pharmacokinetic profile, and particularly its biliary elimination and hepatic disposition, remains undefined. The present study describes an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for 3h (h) with reconstituted blood in a closed circuit; 10 mg of temafloxacin were added to the circulating blood at the onset of the procedure. Bile was recovered throughout the experiments and liver fragments were taken at the conclusion. Assays were carried out by high-performance liquid chromatography. Pharmacokinetic analysis was performed with reference to a monocompartmental open model. Under these conditions, the serum half-life of temafloxacin was 3.1 and the maximal biliary concentration of 19.3 +/- SEM 3.1 micrograms/ml was reached between 30 and 60 min; the cumulative biliary elimination (0-3 h) amounted to 92 +/- 16 micrograms (0.9% of the added dose). Total and hepatobiliary clearances were calculated as respectively 134 and 2.38 ml/h and the hepatobiliary elimination rate as 0.0042 (h-1). At the end of the procedure, 25.7 +/- 3.5% of the added dose of temafloxacin was still present in the circulating blood, and 13.7 +/- 2.4% in the liver. Degradation of the antibiotic in the perfusion device concerned only 2.4% of the dose. The percentage of temafloxacin undergoing hepatic biotransformation, determined by subtraction, was high (57.3%). Under these experimental conditions, temafloxacin appears to be particularly stable in serum, poorly eliminated as parent compound in the bile, highly fixed in the liver and above all subject to a probable hepatic biotransformation. Extrapolation of these experimental data to other species or to the whole organism would be hazardous, but these results should stimulate studies on a possible hepatic metabolism of this new trifluoroquinolone in man.

4-Quinolones↗
PubMed1990

Nifedipine enhances amoxicillin absorption kinetics and bioavailability in humans.

Intestinal absorption of aminopenicillins in vitro uses the dipeptide carrier system. Recent experiments have reported calcium ion to be a cellular mediator of the regulation of electrolyte transport through the enterocyte membrane, especially the Na/H exchange which is partly responsible for the proton gradient energizing the carrier system. In order to assess the in vivo relevance of these data, we studied, in healthy volunteers, the influence of nifedipine, a calcium channel blocking agent, on the intestinal uptake of amoxicillin, a commonly prescribed and well-absorbed aminopenicillin. Results obtained show that 1) intestinal absorption kinetics of amoxicillin follows a zero-order process, which further substantiates the existence of a saturable carrier-mediated process for this antibiotic in humans and 2) calcium channel blockade significantly enhances both absorption rate (by 70%) and bioavailability of amoxicillin (by 21.4%) without modifying its distribution or elimination. These findings might suggest that nifedipine could enhance amoxicillin intestinal uptake by stimulating its active transport.

Adult↗
PubMedDate not supplied

[Kinetics of cefixime biliary clearance in cholecystectomized patients].

Cefixime is an orally administered cephalosporin with physicochemical properties able to account for a possibly significant biliary excretion. In addition, over 50% of total clearance of the drug has been shown to operate through extra renal pathways in healthy volunteers. The aim of the study was to quantify and to delineate the kinetics of cefixime biliary elimination in ten patients provided with external drainage. Following a single 200 mg oral dose of cefixime, biliary clearance of the drug appears to vary from 0.85 to 27.3 ml/min. Contribution of the latter to the apparent total clearance is relatively low since ranging from 0.8 to 18.6% (mean 5%). Additionally, biliary clearance kinetics of the drug proves non linear and well described according to a sigmoidal model. On account of these results, and given the dianionic charge of the molecule as well as the absence of any metabolite reported so far, an intrahepatic binding and accumulating process, mediated by ligandin, seems to underlie the hepatobiliary excretion of cefixime, as previously reported for other anionic beta-lactam antibiotics.

Adult↗